Our ultimate aim is to understand the origin of the electrocardiogram as it arises from cardiac depolarization. We have recently come to question some fundamental assumptions made in attempts to further this understanding. Starting with the paper by Corbin and Scher (Circ. Res. 41: 58-67, 1977) and extending to the paper by Roberts, Hersh and Scher (Circ. Res. 44: 701-712, 1979), we have found that the uniform double layer theory, which is generally applied to the analysis of potentials generated by the heart, is not applicable because cardiac tissue is anisotropic. The velocity of cardiac conduction, the strength of the cells as generators, and the conductivity of the tissue are all anisotropic and are all greater in the direction of the cardiac fibers. We have continued studies in small volumes of myocardial tissue, and have developed an excellent theoretical model which predicts potentials outside a cardiac wavefront. We now intend to extend these studies to larger masses of tissue using the model to predict potentials during depolarization and to compare these with those recorded. These experiments are most important in understanding the origin of the normal and abnormal electrocardiogram. A number of other laboratories have followed our lead in this area.